New properties of old substances
Compound BX-795 successfully fights herpes
Julia Korowski, XX2 century
Herpesviruses, at first glance, are harmless, but they can seriously ruin life. For example, the herpes simplex virus of the first type, affecting the eyes, sometimes causes complications up to blindness. There is no vaccine or medicine that would completely get rid of the virus yet. It is only possible to reduce the frequency, duration and severity of relapses, but the problem is that sometimes herpes is resistant to drugs. We need an alternative, a medicine that would work differently – and perhaps now we have a candidate for this role. Scientific groups from China and the USA conducted parallel studies and came to the conclusion that a substance called BX-795 suppresses the replication of herpes simplex viruses of the first and second types.
Modern medicines for herpes, including acyclovir, penciclovir and others, belong to the group of nucleoside analogues. They prevent the virus from multiplying by suppressing the synthesis of its DNA.
"We have long needed drugs that work with other "targets", because patients who develop resistance to nucleoside analogues do not have many options for treating infection," explains Deepak Shukla, professor at the University of Illinois at Chicago (in a press release A new class of drug to treat herpes simplex virus infection). – We have discovered a molecule that acts in a completely new way. Instead of interacting with the virus, it works with the host cells and helps them get rid of the virus."
The professor and his colleagues were mainly interested in herpes as a cause of eye diseases. Doctors have discovered that a substance called BX-795, which has long been used in laboratory experiments as a PDK1 inhibitor, suppresses the development of infection in human and mouse corneal cells. The researchers were surprised by this discovery because they expected to get the opposite result. The fact is that BX-795 interferes with the work of the enzyme TBK1 (TANK-binding kinase), which is involved in the work of immunity and inflammatory processes. If TBK1 activity is suppressed, the impact of infection is usually exacerbated. But when scientists treated human corneal cells infected with the herpes simplex virus type I (HSV-1) with the compound BX-795, they were soon cleared of infection. "This is not what we expected," comments Tejabhiram Yadavalli, a member of the scientific group.
The compound was effective even in low concentrations, it required 5 times less than existing antiviral drugs. In addition, BX-795 was non-toxic and did not cause the death of healthy cells. "Since BX-795 targets the signaling pathway used by many viruses to reproduce inside cells, it may give rise to a new group of broad–spectrum antiviral drugs," explains Shukla. – Theoretically, with their help, it will be possible to treat other viral infections, including herpes of the second type (HSV-2), which mainly affects the genitals, and HIV. Although so far we have tested BX-795 only on the herpes simplex virus of the first type."
However, American scientists failed to become the first. While they were doing research, another group – from China – has already published a similar work. Moreover, Chinese doctors managed to experiment not only with HSV-1, but also with HSV-2. They confirmed that BX-795 is non-toxic and effectively copes with infection. Both groups concluded that the compound works differently than modern drugs: if acyclovir interacts with the virus directly by embedding itself in its DNA, then the new substance targets the components of the cell itself. However, scientists have not yet agreed on what these components are: researchers from China believe that BX-795 acts on enzymes called "c-Jun-N-terminal kinases" (JNK) and mitogen-activated protein kinase p38, and their colleagues believe that the whole thing is in the family of protein kinases B (AKT). Anyway, we have at least two confirmations that the compound successfully fights herpesviruses. We may even be lucky enough to see the results of clinical trials.
Reports of a possible new antiherpetic drug are particularly interesting in light of studies that have found a link between the herpes virus and Alzheimer's disease.
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